The objective of this study was to achieve the colon-specific delivery of an anti-ulcerative colitis drug using hydroxypropyl methyl cellulose (HPMC) hydrogels. HPMC hydrogels containing poly ethylene glycol (PEG) as cross-links have been prepared by reacting HPMC sodium salt with polyethylene glycol dichloride. The effect of cross-linking agent on swelling behavior of HPMC-PEG hydrogels, were investigated. Swelling parameters such as equilibrium degree of swelling, swelling ratio and network parameter such as molecular mass between cross-links (M(c)) were determined. The cross-linking concentrations were 0.5%, 1%, 1.5%, and 2% (based on weight of HPMC). The equilibrium swelling ratio (Q) of cross-linked HPMC hydrogels increases from 13.2 to 27.1 as the cross-linker percentage increases from 0.5% to 2%. 5-Aminosalicylic acid (5-ASA) was used as a model of an anti-inflammatory drug. Cross-linked HPMC hydrogels were found to be a promising drug delivery system for the drugs to be delivered to the colon.